The accuracy of ACTH as a biomarker for pituitary pars intermedia dysfunction in horses: A systematic review and meta-analysis.
Authors: Meyer James C, Hunyadi László M, Ordóñez-Mena José M
Journal: Equine veterinary journal
Summary
# Editorial Summary: ACTH as a diagnostic biomarker for equine PPID Pituitary pars intermedia dysfunction (PPID) diagnosis relies heavily on baseline ACTH measurement, yet diagnostic accuracy varies considerably across published studies. Meyer and colleagues conducted a systematic review and meta-analysis of 11 studies to quantify ACTH's diagnostic performance and identify sources of heterogeneity using hierarchical summary receiver operating curve and bivariate binomial normal modelling. Pooled results demonstrated moderate sensitivity (72%) but good specificity (88%), with performance declining further when restricted to studies using the common 35 pg/mL threshold (sensitivity 66%, specificity 87%)—meaning baseline ACTH misses approximately one-third of affected horses and produces false-positive results in up to 13% of unaffected populations depending on disease prevalence. The clinical implications are substantial: in a typical practice scenario with 20% PPID prevalence, practitioners can expect roughly 104 false positives and 68 false negatives per thousand horses tested, making ACTH unreliable for screening or confirming diagnosis in horses without clinical signs. The authors recommend ACTH as a potential "rule-in" test only in horses with high pretest probability of PPID, and highlight that study design, reference standards and threshold selection significantly influence accuracy—underscoring the need for better-controlled diagnostic research before standardising testing protocols across the profession.
Read the full abstract on PubMed
Practical Takeaways
- •Use baseline ACTH as a 'rule-in' test only in horses with clinical signs suggestive of PPID and high pre-test probability of disease—do not use for screening asymptomatic horses
- •Be aware that a single negative ACTH result does not reliably exclude PPID (sensitivity 66-72%), so additional diagnostic testing or seasonal retesting may be warranted in clinically suspicious cases
- •Standardised ACTH thresholds (e.g. 35 pg/mL) improve consistency, but expect substantial variation in diagnostic performance depending on laboratory methods and reference population
Key Findings
- •Baseline ACTH demonstrated sensitivity of 0.72 (95% CI: 0.62-0.82) and specificity of 0.88 (95% CI: 0.79-0.93) across 11 studies for PPID diagnosis
- •When restricted to studies using 35 pg/mL ACTH threshold (n=6), sensitivity decreased to 0.66 (95% CI: 0.54-0.77) with specificity of 0.87 (95% CI: 0.74-0.94)
- •At 2% disease prevalence, ACTH testing produces 127 false positives per 1,000 horses; at 90% prevalence, produces 306 false negatives per 1,000 horses
- •Significant heterogeneity and bias detected in included studies; case-control design and clinical reference standards improved diagnostic accuracy